Neuropediatrics 2005; 36(4): 246-251
DOI: 10.1055/s-2005-865773
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Congenital Myopathy with Arrest of Myogenesis Prior to Formation of Myotubes

U.-P. Ketelsen1 , B. Brand-Saberi2 , B. Uhlenberg3 , M. Wagner4 , H.-G. Laberke4 , H. Omran1
  • 1Department of Neuropediatrics and Muscle Disorders, Neuromuscular Pathology, Albert-Ludwigs-University, Freiburg, Germany
  • 2Department of Anatomy, Albert-Ludwigs-University, Freiburg, Germany
  • 3Department of Neuropediatrics, Charité, Humboldt University, Berlin, Germany
  • 4Olga Hospital, Stuttgart, Germany
Further Information

Publication History

Received: January 31, 2005

Accepted after Revision: May 15, 2005

Publication Date:
22 August 2005 (online)

Abstract

We report a novel type of congenital myopathy, which is characterized by an early arrest of muscle formation prior to formation of myotubes. A female infant born prematurely at 32 weeks of gestational age died after six weeks of continuous ventilatory support. Various muscle specimens including quadriceps, deltoid, pectoral, neck, psoas, tongue, and diaphragm musculature were studied. Light and electron microscopy revealed well-demarcated fascicular structures interspersed with undifferentiated, mononuclear myogenic cells. Multinucleated myotubes and muscle fibres were not detectable, pointing towards a defect prior to the generation of myotubes during myogenesis. Immunohistochemistry identified the absence of dystrophin, N-CAM, MyoD and myogenin expression in these myogenic cells, compatible with a block of the complex transcriptional network necessary for correct embryonic muscle formation at an early stage of muscle development. These myopathological findings were absent in cardiac muscle, indicating that the defect exclusively affects skeletal muscle formation.

References

  • 1 Braun T, Arnold H H. Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal muscle development.  EMBO J. 1995;  14 1176-1186
  • 2 Christ B, Ordahl C P. Early stages of chick somite development.  Anat Embryol (Berl). 1995;  191 381-396
  • 3 Goulding M, Lumsden A, Paquette A J. Regulation of Pax-3 expression in the dermomyotome and its role in muscle development.  Development. 1994;  120 957-971
  • 4 Hasty P, Bradley A, Morris J H. et al . Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene.  Nature. 1993;  364 501-506
  • 5 Jostes B, Walther C, Gruss P. The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system.  Mech Dev. 1990;  33 27-37
  • 6 Kablar B, Krastel K, Ying C. et al . MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle.  Development. 1997;  124 4729-4738
  • 7 Kiefer J C, Hauschka S D. Myf-5 is transiently expressed in non-muscle mesoderm and exhibits dynamic regional changes within the presegmented mesoderm and somites I - IV.  Dev Biol. 2001;  232 77-90
  • 8 Muntoni F, Brown S, Sewry C, Patel K. Muscle development genes: their relevance in neuromuscular disorders.  Neuromuscular Disord. 2002;  12 438-446
  • 9 Nabeshima Y, Hanaoka K, Hayasaka M. et al . Myogenin gene disruption results in perinatal lethality because of severe muscle defect.  Nature. 1993;  364 532-535
  • 10 Noden D M, Marcucio R, Borycki A G, Emerson C P. Differentiation of avian craniofacial muscles: I. Patterns of early regulatory gene expression and myosin heavy chain synthesis.  Dev Dyn. 1999;  216 96-112
  • 11 North K, Goebel H H. Congenital myopathies. Jones Jr HR, De Vivo DC, Darras BT Neuromuscular Disorders of Infancy, Childhood, and Adolescence. A Clinician's Approach. Oxford; Butterworth/Heinemann, Elsevier Science 2003: 601-633
  • 12 Patapoutian A, Yoon J K, Miner J H. et al . Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome.  Development. 1995;  121 3347-3358
  • 13 Pourquie O. Vertebrate somitogenesis.  Annu Rev Cell Dev Biol. 2001;  17 311-350
  • 14 Pownall M E, Gustafsson M K, Emerson C P. Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos.  Annu Rev Cell Dev Biol. 2002;  18 747-783
  • 15 Puri P L, Sartorelli V. Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and posttranscriptional modifications.  J Cell Physiol. 2000;  185 155-173
  • 16 Wang Y, Schnegelsberg P N, Dausman J, Jaenisch R. Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin.  Nature. 1996;  379 823-825
  • 17 Zhang W, Behringer R R, Olson E N. Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies.  Genes Dev. 1995;  9 1388-1399

MD Heymut Omran

Department for Pediatric Neurology and Muscle Disorders
University Hospital

Mathildenstrasse 1

79106 Freiburg

Germany

Email: omran@kikli.ukl.uni-freiburg.de